Lancet
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Currently licenced direct oral anticoagulants selectively target thrombin (eg, dabigatran) or coagulation factor Xa (eg, apixaban, betrixaban, edoxaban, and rivaroxaban). Designed to be given in fixed doses without routine monitoring, direct oral anticoagulants have a lower propensity for food and drug interactions than do vitamin K antagonists, and in randomised controlled trials involving around 250 000 patients, they were at least as effective for prevention and treatment of thrombosis and were associated with a lower risk of life-threatening bleeding. The absolute benefits of direct oral anticoagulants over vitamin K antagonists are modest; however, guidelines recommend them in preference to vitamin K antagonists for most indications because of their ease of use and superior safety. ⋯ Direct oral anticoagulants are contraindicated in patients with mechanical heart valves and should be used with caution or avoided in patients with advanced kidney or liver disease. In this Therapeutics paper, we review the pharmacology of direct oral anticoagulants, summarise the evidence that led to their approval and incorporation into treatment guidelines, and explore key unresolved issues. We also briefly discuss future perspectives for the development of oral anticoagulants.
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Gastrointestinal symptoms are highly prevalent, but many people who have them will have no organic explanation for their symptoms. Most of these people will be labelled as having a functional gastrointestinal disorder, such as irritable bowel syndrome, functional dyspepsia, or functional constipation. These conditions affect up to 40% of people at any one point in time, and two-thirds of these people will have chronic, fluctuating symptoms. ⋯ Symptom-based criteria are used to make a diagnosis, with judicious use of limited investigations in some patients. The general principles of treatment are based on a biopsychosocial understanding and involve management of physical symptoms and, if present, psychological comorbidity. In the future, treatment approaches to functional gastrointestinal disorders are likely to become more personalised, based not only on symptoms but also underlying pathophysiology and psychology.
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The clinical benefit of LDL cholesterol lowering treatment in older patients remains debated. We aimed to summarise the evidence of LDL cholesterol lowering therapies in older patients. ⋯ None.
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Dyspepsia is a complex of symptoms referable to the gastroduodenal region of the gastrointestinal tract and includes epigastric pain or burning, postprandial fullness, or early satiety. Approximately 80% of individuals with dyspepsia have no structural explanation for their symptoms and have functional dyspepsia. Functional dyspepsia affects up to 16% of otherwise healthy individuals in the general population. ⋯ Other therapies with evidence of effectiveness include proton pump inhibitors, histamine-2 receptor antagonists, prokinetics, and central neuromodulators. The role of psychological therapies is uncertain. As our understanding of the pathophysiology of functional dyspepsia increases, it is probable that the next decade will see the emergence of truly disease-modifying therapies for the first time.
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Irritable bowel syndrome is a functional gastrointestinal disorder with symptoms including abdominal pain associated with a change in stool form or frequency. The condition affects between 5% and 10% of otherwise healthy individuals at any one point in time and, in most people, runs a relapsing and remitting course. The best described risk factor is acute enteric infection, but irritable bowel syndrome is also more common in people with psychological comorbidity and in young adult women than in the rest of the general population. ⋯ The mainstays of treatment include patient education about the condition, dietary changes, soluble fibre, and antispasmodic drugs. Other treatments tend to be reserved for people with severe symptoms and include central neuromodulators, intestinal secretagogues, drugs acting on opioid or 5-HT receptors, or minimally absorbed antibiotics (all of which are selected according to predominant bowel habit), as well as psychological therapies. Increased understanding of the pathophysiology of irritable bowel syndrome in the past 10 years has led to a healthy pipeline of novel drugs in development.